Microvascular shear rate is disrupted with elevated tissue bath glucose in normal mice.

Abstract

Blood glucose levels reflect interstitial glucose in both diabetics and normal patients. Long term elevated blood glucose adversely affects microvascular responses linked to shear sensing. We hypothesized that elevated interstitial glucose levels alone in non-diabetic mice would disrupt axial gradients in SR. In prior work, we demonstrated axial gradients in shear rate (SR) both along the length of arteriolar networks, and within bifurcation regions for sequential arteriolar branches. Networks were observed in the cremaster muscle of anesthetized (pentobarbital 50mg/kg, n=6) C57BL/6 mice during control (Ctl, 0 Glc) and with excess interstitial glucose (Glc, 270 mg/dL=15 mM, 2 h, bath). Diameter (D) and fluorescent red blood cell (RBC) velocity (V) were measured for sequential bifurcations. SR was calculated as: 8V/D for feed and branch segments of each bifurcation. For time controls, SR was lower for the feed segments (206±96/s, means±SD) compared to all branches, with the SR in the upstream branches (441±597/s) higher and more variable than in the last branch of the network (207±24/s), as expected. With Glc SR decreased precipitously along the feed (31±7/s). All cell flux was diverted from upstream branches to the last branch of the network, where SR was 100±80/s; in some cases transient flow reversal was noted in upstream branches, meaning that RBCs were being drawn from capillary networks back to the central arteriolar feed and thence diverted to the last branch of the network. Feed D dilated (Ctl 9±2 μm; Glc 14±4 μm), but branch D (Ctl 6±1; Glc 8±1 μm) was unaffected by glucose; thus changes in SR were not attributed to changes in resistance alone. We conclude that only 2 hours of unregulated glucose levels significantly adversely affect flow distribution and axial gradients in shear within this muscle preparation. (NIH DK68401)